Clinical Trial: Safety and Effectiveness of 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) to Treat Idiopathic Intracranial Hypertension.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Lowering Intracranial Pressure in Idiopathic Intracranial Hypertension: Assessing the Therapeutic Efficacy and Safety of an 11β-hydroxysteroid Dehydrogenase Type 1 In

Brief Summary:

Assessing the safety and effectiveness of a 11-βhydroxysteroid dehydrogenase type 1 inhibitor (AZD4017), in a placebo controlled trial, in acute idiopathic intracranial hypertension (IIH) IIH is a condition of young, overweight women with characteristic raised intracranial pressure (pressure around the brain) leading to papilloedema (swelling of the nerve supplying the eye), visual loss and headaches. Medical literature (Cochrane review) demonstrates there is little evidence for the treatments used for IIH. Weight control appears the most effective method of improving symptoms but weight loss is difficult to maintain. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme which regulates local steroid levels and our previous research suggests it may influence the production of brain fluid(cerebrospinal fluid or CSF). 11β-HSD1 levels fall with weight loss and this is associated with with decreased intracranial pressure.

Our primary outcome is to determine whether AZD4017, an inhibitor of 11β-HSD1, will reduce the pressure in the brain and as a consequence improve IIH. Patients are eligible to enter the study if they are between 18-55 years old with acute (<6 months) IIH, signs of active disease (papilloedema and raised CSF pressure (>25 cmH20)), no other major illnesses and have no plans for pregnancy during the study period.

This is an MRC funded single centre, phase II, double-blinded, randomised control drug trial. It will be conducted at the University Hospital Birmingham and the University of Birmingham will act as Sponsor. Eligible participants will be randomly assigned to AZD4017 or a placebo ('dummy' with no active drug) for 3 months with a follow up a month later. Investigations during the study will include bloods, urine samples, pregnancy tests, lumbar punctures, DXA scans

Detailed Summary:
Sponsor: University of Birmingham

Current Primary Outcome: Intracranial Pressure [ Time Frame: 12 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• IIH Symptoms [ Time Frame: 16 weeks ]
  To examine the temporal change in IIH symptoms (presence or absence of tinnitus, visual loss, diplopia, visual obscurations, and headache).
• Visual function [ Time Frame: 16 weeks ]
  To examine the temporal change in IIH visual function in both eyes (measured by LogMAR (log of the minimum angle of resolution) chart to assess visual acuity, automated perimetry (Humphrey 24-2 central threshold) to measure the visual field mean deviation and a Pelli-Robson chart to evaluate contrast sensitivity) between the baseline to week 12 and 4 weeks following treatment (follow-up visit).
• Papilloedema [ Time Frame: 16 weeks ]
  To examine the temporal change in papilloedema (evaluated using, 1) spectral optical coherence tomography (Stratus OCT V4.0.1, Carl Zeiss, Meditec, Welwyn Garden City) and, 2) stereoscopic fundus photographs with Frisen classification (by masked neuro-ophthalmologists) to grade the images) between the baseline to week 12 and to week 16 (follow-up visit).
• Headache-associated disability [ Time Frame: 16 weeks ]
  To examine the changes in headache associated disability through the headache impact test-6 score (HIT 6) and the headache index score (sum of product of daily severity (1-5) and duration (in hours) divided by frequency over 7 days) between the baseline and 12 weeks with a further analysis between week 12 and 16.
• Anthropometric measurements (waist/hip) [ Time Frame: 12 weeks ]
  To examine the temporal change in waist/hip ratio (waist and hip measured in cm) over 12 weeks of treatment.
• Anthropometric measurements (BP) [ Time Frame: 12 weeks ]
  To examine the temporal change in blood pressure (in mmHg) over 12 weeks of treatment.
• Anthropometric measurements (BMI) [ Time Frame: 12 weeks ]
  To examine the temporal change in Body Mass Index (in kg/m2) over 12 weeks of treatment.
• Adverse events [ Time Frame: 16 weeks ]
  To examine the safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.

Original Secondary Outcome:

• IIH Symptoms [ Time Frame: 16 weeks ]
  To examine the temporal change in IIH symptoms (presence or absence of tinnitus, visual loss, diplopia, visual obscurations, and headache).
• Visual function [ Time Frame: 16 weeks ]
  To examine the temporal change in IIH visual function in both eyes (measured by LogMAR (log of the minimum angle of resolution) chart to assess visual acuity, automated perimetry (Humphrey 24-2 central threshold) to measure the visual field mean deviation and a Pelli-Robson chart to evaluate contrast sensitivity) between the baseline to week 12 and 4 weeks following treatment (follow-up visit).
• Papilloedema [ Time Frame: 16 weeks ]
  To examine the temporal change in papilloedema (evaluated using, 1) spectral optical coherence tomography (Stratus OCT V4.0.1, Carl Zeiss, Meditec, Welwyn Garden City) and, 2) stereoscopic fundus photographs with Frisen classification (by masked neuro-ophthalmologists) to grade the images) between the baseline to week 12 and to week 16 (follow-up visit).
• Headache-associated disability [ Time Frame: 16 weeks ]
  To examine the changes in headache associated disability through the headache impact test-6 score (HIT 6) and the headache index score (sum of product of daily severity (1-5) and duration (in hours) divided by frequency over 7 days) between the baseline and 12 weeks with a further analysis between week 12 and 16.
• Anthropological measurements [ Time Frame: 12 weeks ]
  To examine the temporal change in anthropological measures (blood pressure, BMI, waist/hip ratio and DXA scan to assess body composition) over 12 weeks of treatment.
• Adverse events [ Time Frame: 16 weeks ]
  To examine the safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.

Dates:
Date Received: December 16, 2013
Date Started: April 2014
Date Completion:
Last Updated: May 4, 2017
Last Verified: May 2017